Process for the preparation of stilbene derivatives



Patented Sept. 28, 1 954 UNITED STATES PATENT OFFICE PROCESS FOR THEPREPARATION OF STILBENE DERIVATIVES Leslie Noel Savidge and RichardThomas, Bromborough, England, assignors to Lever Brothers Company, NewYork, N

Maine Y., a corporation of No Drawing. Application July 26, 1950, SerialNo. 176,068

Claims priority, application Great Britain April 3, 1947 15 Claims.

011)," to materials, particularly cotton, linen and other cellulosicmaterials, blue fluorescent effects by incorporating in the materials asmall proportion of a compound of the general formula:

(R)m $03M)" in which each R and R is a hydrocarbon radical, such asalkyl, aryl or aralkyl, lower alkyl groups of from 1 to 4 carbon atomsbeing preferred; each :0 and x is zero or a small integer such as l, 2,3, or the like; each n, n, m and m is an integer expressing the numberof the respective groups substituted in the respective benzene rings,such 4 as 1, 2, 3, 4 and the like (the maximum number being thepositions on the benzene rings which are not otherwise substituted) andeach M and M is hydrogen or a cation such as sodium, potassium,ammonium, or the like; each Y and Y is hydrogen or a substituent such asalkyl, i. e., methyl or ethyl, acylamino, i. e., acetylamino, and thelike. The components do not contain any free (primary) amino groupsdirectly attached to any benzene ring, since the presence of such groupsrenders the compounds unstable to light, air and oxygen. Any of thebenzene rings may contain substituents (except as specified above), suchas methyl, acetylamino, and the like. Salts, such as the sodium salt,are most convenient to use in practice.

The present invention provides a method of preparing compounds of theabove type, which comprises bringing together under reactive conditionsan amino stilbene compound having the general formula:

and an acyl chloride having the general formula:

(ROLF-@0001 and after reaction thereof to produce a product having thegeneral formula:

recovering the product. In the above scheme,

.. each R is a hydrocarbon radical, such as alkyl,

aryl or aralkyl, lower alkyl groups of from 1 to 4 carbon atoms beingpreferred, each M and M is som'n' 012%.

hydrogen or a cation, such as sodium, potassium, ammonium or the like,each at and m is zero or a small integer, such as l, 2, 3, or the like,each n, n and m is a small integer expressing the number of therespective groups substituted in the respective benzene rings (themaximum number being the positions on the benzene rings which are nototherwise substituted). Any of the benzene rings may contain furthersubstituents, such as methyl, acylamino and the like. Where a product isdesired having acylamino groups in the terminal benzene rings, thecorresponding nitroalkoxybenzoyl chloride should be used in the reactionand the nitro-groups of the resulting compound reduced to amino-groupswhich are then acylated.

The reaction is carried out in solution in bases such as pyridine,quinoline or piperidine, or in mixtures of these bases and water. If therate of hydrolysis of the acyl chloride is slow, compared to the rate ofreaction thereof with the 4,4-diamino-stilbene compound, the reactionmay be carried out in aqueous media. If, however, the hydrolysisreaction is rapid, a large quantity of the acyl chloride may be lostthereby since reaction between product of hydrolysis, the correspondingacid, and the aminostilbene compound does not occur; under thesecircumstances, there- In general outline, when the reaction is carriedout in aqueous basic media, the preferred method of procedure issubstantially as follows: The 4,4-diaminostilbene-disulfonic acid isdissolved or suspended in water and sodium carbonate added until themixture becomes alkaline. The acyl chloride, dissolved in the base, isthen added to the mixture over a short period. The mixture is thenheated under reflux until acylation is complete.

If insumcient sodium carbonate and/or organic base has been added at thestart of the reaction, the solution will become acid as a result ofliberation of hydrogen chloride. To precipitate the sulfonic acid, thesolution is concentrated, acidified and cooled. To recover the sodiumsalt of the 4,4'-diamidostilbene mixture, the mixture is made alkalineagain with sodium carbonate or hydroxide. The sodium salt precipitatesfrom solution on cooling if the solution is suificiently concentrate'dand is recovered by filtration or centrifuging. The crudemate'rial maybe recrystallized from hot aqueous pyridine.

WW: 119 reaction is to becarried out in nonaqueous basic media, such aspyridine, in general outline the preferred procedure is as follows: The4.,4-diaminostilbenedisulfonic acid is dissolved pyridine and the acylchloride added thereto. Reaction is completed by heating, prefer blyunder reflux, and the pyridine salt of the diamidostilbene-di sulfonicacid acidified by addition of aqueous hydrochloric acid in sufiicientaniornt to precipitate the diamidosulfonic acid, which isthen-separated. The sodium salt of the may then be formed by dissolvingthe acid in suificient sodium carbonate or hydroxide solution tocompletely neutralize the sulfonic acid groups. lhe sodium salt is thenrecovered from the mixture and may be recrystallized with aqueouspyridine as before.

Any desired metal salt of the sulfonate may be formed by adding thepyridine salt of the diamido stilbenedisulphonic acid to an aqueoussolution of a water-soluble salt of the corresponding metal.

In order to facilitate a clear understanding of the invention, thefollowing specific examples of preparing certain compounds will now bedescribed:

Example 1 4,4-diaminostilbene-2,2'-disulfonic acid (23 g. :0.062 mole)was stirred and heated with water (150 cc.) and sodium carbonate (5 g.).When the solution boiled, more sodium carbonate was added until themixture became alkaline. p- Anisoyl chloride (21 g.:'0.124 mole) in purepyridine (50 cc.) was added during a period of a few minutes and themixture heated under reflux for one hour. The liquid was made alkalineonce more with sodium carbonate and cooled. The product was recovered byfiltration, and washed with water until it was a pale orange color. Thematerial was dissolved in hot aqueous pyridine (80:20; 2.5 liters)decolorized and filtered. On cooling the solution the product wasobtained 4 as a pale yellow crystalline powder. This was thoroughlywashed with hot water and dried. Yield, 14 g. (approximately 35%). Theproduct was sodium 4,4di(p-methoxy) benzoylaminostilbone-2,2-disulfonate:

NHC 0-00 cm SOaNa OaNB- The m methoxy isomer may be prepared by the sameprocedure using the m-anisoyl chloride.

Example 2 A mixture of o cresol (108 g.) water (300 cc.), potassiumhydroxide (336 g.), carbon tetrachloride (180 g.), ethyl alcohol cc.)and copper bronze (0.3 g.), which darkened slowly, was heated underreflux for nine hours on a steam bath. The excess carbon tetrachloridewas then distilled off, together with part of the alcohol. The cooled,filtered residue, which had a deep red color, was acidified andextracted with ether. The combined etheral extracts were then washedwith a saturated solution of sodium bisulfite (this treatment partiallyremoves the ketonic byproduct responsible for the red color of the ethersolution). Subsequently the ether solution was extracted with sodiumbicarbonate, and the combined aqueous extracts acidified withhydrochloric acid. The crude acid which precipitated was separated andrecrystallized from hot water with the addition of charcoal. Afterrecrystallization the product, a-hydroxy- 3 -methyl-benzoic acid, had amelting point of 170=173 C. Yield 74 g. (50%). p I

4-h'ydroxy-3=met'hylbenzoic acid (40 g.) was dissolved in water (500cc.) containing sodium hydroxide (22 g.). Dimethyl sulfate (2'? cc.) wasadded to the warm solution and the whole vigorously shaken. Furtheralternate additions of dime'thyl sulfate and concentrated sodiumhydroxide solution were necessary before methylation was complete. Inall, a total of 63.5 cc. of dimethyl sulfate was required. The mixturewas acidified to precipitate the product, 4-methoxy- 3-'nethyl benzoicacid, which, after crystallization from alcohol, had a melting point of193 C. Yield 39 g. (90%).

4-methoxy-3-m-ethyl benzoic acid (10 g.) was heated under reflux withthionyl chloride (7 cc.) and benzene (30 cc.) until there was no furtherevolution of hydrogen chloride. The benzene and excess thionyl chloridewere removed by distillation and the residue, after being kept oversodium hydroxide to remove traces of thionyl chloride, was fractionated,that portion having B. P. C./2() mm. being collected. Yield 9.15 g.(85%) of acolorless solid, 4-methoxy-3-methyl benzoyl chloride, ofmelting point 36 C. Alternatively, the crude material may becrystallized from petroleum naphtha (pentane) as a pink solid.

r-methoxy-ii-methylbenzoyl chloride (5 g.) was added to4,4'-diaminostilbene-2,2disulfonic acid (4 g.) and pyridine (10 00.).The mixture immediately became warm, and reaction appeared to becomplete after heating on the steam bath for one-quarter hour. Thepyridine was, however, finally boiled by placing the mixture in an oilbath for one hour. (A test portion dissolved in water produced no colorwith sodium hypo- 'chlorite solution.) Water was added and alsosufiioient hydrochloric acid to precipitate the product, which wasseparated by filtration. The crude material was then stirred with sodiumhyfurther purification the product, p-ethoxybenzyl chloride, was used inthe next stage.

4,4-diaminostilbene-2,2-disulfonic acid (4 g.) in water (64 cc.) wasjust neutralized at the boil with sodium carbonate. To the hot solution,p-ethoxybenzoyl chloride (4.4 g.) in pyridine cc.) was added all atonce. The product was worked up by filtration and washing, and finallyrecrystallized from aqueous pyridine. It was ob- CH3 oaNa AOBNQ Similarmethods may be used to prepare other isomeric methyl methoxy compounds,using the corresponding acyl chlorides.

cane-O0 ONE-- Example 3 Sodium 4,4-di(o-1nethoxy)benzoylaminostilbene-2,2-disulfonate tained as a pale yellowmicrocrystalline powder. Yield 2 g. Theproduct was sodium 4,4-di(p-ethoxy) benzoylaminostilbene-2,2-disulfonate:

OaNa AOsNa The 0- and m-ethoxy isomers may be prepared by similarprocedures, using 0- and m-ethoxy benzoyl chloride.

5GB} OaNa osNa OCHa was prepared by a similar method to that usedExample 5 in Example 2, using o-anisoyl chloride instead of S odium 4,4d1(3,4,5 trimethoxy) benzoyl- 4-methoxy-3-methylbenzoyl chloride.aminostflbeneaz, disulfonate CHaO 0on3 CHM-O0ONH OH=CH'NHCOOCHa CHaAOsNa OaNa CHa Example 4 was prepared according to the method of Example2, using 3,4,5-t1'imethoxy benzoyl chloride instead or"4-methoxy-3-methylbenzoyl chloride. Similarly, other trimethoxy andhigher trialkoxy isomers may be prepared from the corresponding alkoxybenzoyl chlorides.

Example 6 Sodium 4,4-di(p-phenoxy) bene-2,2'-disulfonatehenzoylaminostilsolution. Suflicient strong sodium hydroxide solutionwas added to give a strongly alkaline reaction and the mixture washeated under reflux for one-half hour, after which it was cooled andacidified. The crude dry product, p-ethoxybenzoic acid, Wasrecrystallized from benzene/alcohol (:56 mixture: approximately 100 cc.)and gave S OsNa shiny plates, M. P. 198 C. Yield 11 g.

0 aNa S O 3N8.

was prepared according to the method of Example 4, using p-phenoxybenzoyl chloride instead of p-ethoxy benzoyl chloride.

Emample 7 Sodium 4,4'-di(p-benzyloxy)benzoylaminostilbene-2,2'-disulfonate OaNa was prepared according to themethod of Examp-Ethoxybenzoic acid (4 g.) prepared as above ple 4, usingp-benzyloxy benzoyl chloride instead was heated under reflux withthionyl chloride (4 g.) in benzene (20 cc.) until there was no furtherloss of hydrogen chloride. The benzene was removed and the residue,which rapidly solidiof p-ethoxy benzoyl chloride.

Example 8 Sodium 4,4-di(3,4-dimethoxy) benzoylaminofied while still hot,was kept over caustic soda stilbene-2,2-disulfonate to remove traces ofthionyl chloride.

Without AOaNa AOQNQ CH3 was prepared according to the method of Example2, using 3,4-dimethoxy benzoyl chloride instead of4-methoxy-S-methylbenzoyl chloride.

SOaNa Likewise, the other isomeric dimethoxy compounds may be preparedfrom the corresponding dimethoxy benzoyl chlorides.

Example 9 4-methoxy-3-nitrobenzoic acid (1.5 g.), benzene cc.) andthionyl chloride (3 cc.) were heated at the boil for 30 minutes. Theexcess thionyl chloride and benzene were removed by distillation invacuo, and the residue of crude i-methoxy-ii-nitrobenzoyl chloridesolidified on cooling,

yielded sodium 4,4-di-(p-methoxybenzoylamino) benzoylaminostilbene-2,2-disulfonate CHaO-OCONH-OCONHOGH=CH as pale greenish-yellowmircocrystalline needles.

Yield 0. 1 g. (approx. 70%).

We claim: 1. The method which comprises reacting an amino stilbenecompound having the formula:

INT-GOO NH armors-QM; Od-O-NH H l.

SOaM 03M in the presence of an organic nitrogen base as a solvent andacid acceptor to produce a product purification, were mixed with 4:-1-diaminosti1- having the formula:

bene-2:2-disulionic acid (1.5 g.) and anhydrous pyridine (10 cc.) andheated on a steam-bath for 2 hours. Water was then added and the mixtureacidified with hydrochloric acid to precipitate 4,4'-di- (4-methoxy-3"-nitro) -benzoylaminostilbene-2,2-disulionic acid.

The damp solid obtained after filtration was reduced, without furtherpurification, by the addition of iron filings (3 g.) and acetic acid (2000.). After boiling for 2 hours, more iron (2 g.) was added and heatingcontinued for a further 2 hours. The mixture was then diluted with waterand made alkaline by the addition of sodium carbonate and filtered atthe boil. Sodium 4,4=-di-(e-methoxy-3 amino)benzoylaminostilbene-2,2-disulfonate crystallised from the cooledfiltrate as a pale yellow microcrystalline powder. Yield 2 g. (approx.65%).

1 g. of product was mixed with acetic anyhydride (10 cc.) and sodiumacetate (1.5 g.) and heated for 6 hours under r flux. After pouring thereaction mixture on to ice and water and making alkaline by the additionof sodium hydroxide, the crude product was obtained by filtration.crystallisation from aqueous pyridine yielded sodiumLi-dict"-nethoxy-3-acetylamino) -benzoylaminostilb aloe-2,2 -disulfonateNH.CO.CH3 OaNa as a grcyish yellow microcrystalline powder. Yield 1 g.(approx. 95%).

Example 10 where R in the above formulae is selected from the groupconsisting of alkyl radical of 1 to 4 carbon atoms, phenyl and benzyl; Mis selected from the group consisting of hydrogen, sodium, potassium andammonium; :c is selected from the group consisting of zero and one; Y isselected from the group consisting of hydrogen, lower alkyl, and nitrogroups; and m is a small integer selected from the group consisting of1, 2 and 3.

2. The method according to claim 1 in which the acyl chloride is amethoxybenzoyl chloride.

3. The method in accordance with claim 1 in which the base is pyridine.

4. The method in accordance with claim 1 in which the compounds arebrought together in solution in an aqueous base.

5. The method in accordance with claim 4 in which the compounds arebrought together in a mixture of water and pyridine.

6. The method in accordance with claim 1 in which the acyl chloride isan anisoyl chloride.

'7. The method in accordance with claim 6 in which the anisoyl chlorideis p-anisoyl chloride.

8. The method according to claim 6 in which the anisoyl chloride iso-anisoyl chloride.

9. The method according to claim 1 in which SOaNa NH.CO.CH2

the acyl chloride is a dimethoxybenzoyl chloride.

10. The method according to claim 9 in which the acyl chloride is 3,4dimethoxybenzoyl chloride.

11. The method according to claim 1 in which the arm'ncstilbene compoundis 4,4-diaminostilbene-2,2-disulfonic acid.

12. The method according to claim 1 in which the acyl chloride is3-methyl-4-methoxybenzoyl chloride.

13. The method according to claim 1 in which the acyl chloride is3-nitro-4-meth0xybenzoyl chloride.

14. The method according to claim 13 in which References Cited in thefile of this patent Number UNITED STATES PATENTS Name Date Eberhart eta1. Apr. 26, 1949 Lubs et a1. Feb. 14, 1950 Lubs et a1. Feb. 14, 1950Hausermann Sept. 5, 1950

1. THE METHOD WHICH COMPRISES REACTING AN AMINO STILBENE COMPOUND HAVINGTHE FORMULA: